Quality assurance of radiotherapy in the ongoing EORTC 22042–26042 trial for atypical and malignant meningioma: Results from the dummy runs and prospective individual case Reviews

BACKGROUND: The ongoing EORTC 22042–26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study. MATERIAL/METHODS: Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (http://atc.wustl.edu/) and were assessed prospectively. RESULTS: Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR’s results did not predict for an improved QA process in accrued brain tumor patients. CONCLUSIONS: A substantial number of protocol deviations were observed in this prospective QA study. The number of cases accrued per institution was a significant determinant for protocol deviation. These data suggest that successful DR is not a guarantee for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations

Strategies for recruitment and retention of teen mothers in a program to prevent repeat pregnancy

Background: We describe challenges to recruitment and retention of teen mothers in a study to prevent repeat teen pregnancies, and strategies used to overcome them. Methods: We documented recruitment efforts, the teens who were retained at each stage of the intervention and changes to strategies. Results: Challenges to recruitment and retention were related to lifestyles, immaturity, and competing demands, among others. Successful strategies included bus advertisements, early pairing of teens with mentors, using electronic media, convenient meeting times with a meal, providing child care, transportation vouchers and immediate incentives. Conclusions: This study highlights impediments to teen mother research recruitment and retention, and the value of emerging technologies and strong bonding relationships early in the intervention to maximize recruitment and retention

Endocarditis after Use of Tongue Scraper

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self-evaluative judgment about cognition in AD. Impaired self-evaluation was related to a decrease in brain metabolism measured with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self-referential processes and perspective taking in AD

Performance Measures Based on How Adults With Cancer Feel and Function: Stakeholder Recommendations and Feasibility Testing in Six Cancer Centers

PURPOSE Patient-reported outcome measures (PROMs) that assess how patients feel and function have potential for evaluating quality of care. Stakeholder recommendations for PRO-based performance measures (PMs) were elicited, and feasibility testing was conducted at six cancer centers. METHODS Interviews were conducted with 124 stakeholders to determine priority symptoms and risk adjustment variables for PRO-PMs and perceived acceptability. Stakeholders included patients and advocates, caregivers, clinicians, administrators, and thought leaders. Feasibility testing was conducted in six cancer centers. Patients completed PROMs at home 5-15 days into a chemotherapy cycle. Feasibility was operationalized as $75$ 75% patient acceptability. RESULTS Stakeholder priority PRO-PMs for systemic therapy were GI symptoms (diarrhea, constipation, nausea, vomiting), depression/anxiety, pain, insomnia, fatigue, dyspnea, physical function, and neuropathy. Recommended risk adjusters included demographics, insurance type, cancer type, comorbidities, emetic risk, and difficulty paying bills. In feasibility testing, 653 patients enrolled (approximately 110 per site), and 607 (93%) completed PROMs, which indicated high feasibility for home collection. The majority of patients (470 of 607; 77%) completed PROMs without a reminder call, and 137 (23%) of 607 completed them after a reminder call. Most patients (72%) completed PROMs through web, 17% paper, or 2% interactive voice response (automated call that verbally asked patient questions). For acceptability, . 95% of patients found PROM items to be easy to understand and complete. CONCLUSION Clinicians, patients, and other stakeholders agree that PMs that are based on how patients feel and function would be an important addition to quality measurement. This study also shows that PRO-PMs can be feasibly captured at home during systemic therapy and are acceptable to patients. PRO-PMs may add value to the portfolio of PMs as oncology transitions from fee-for-service payment models to performance-based care that emphasizes outcome measures

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Internet-based self-help treatment for depression in multiple sclerosis: study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression in MS patients is frequent but often not treated adequately. An important underlying factor may be physical limitations that preclude face-to-face contact. Internet-based treatment showed to be effective for depressive symptoms in general and could thus be a promising tool for treatment in MS.</p> <p>Methods/design</p> <p>Here, we present a study protocol to investigate the effectiveness of a 5 week Internet-based self-help problem solving treatment (PST) for depressive symptoms in MS patients in a randomized controlled trial. We aim to include 166 MS patients with moderate to severe depressive symptoms who will be randomly assigned to an Internet-based intervention (with or without supportive text-messages) or waiting list control group. The primary outcome is the change in depressive symptoms defined by a change in the sum score on the Beck Depression Inventory (BDI-II). Secondary outcomes will include measures of anxiety, fatigue, cognitive functioning, physical and psychological impact of MS, quality of life, problem solving skills, social support, mastery, satisfaction and compliance rate. Assessments will take place at baseline (T0), within a week after the intervention (T1), at four months (T2) and at ten months follow-up (T3: only the intervention group). The control group will be measured at the same moments in time. Analysis will be based on the intention-to-treat principle.</p> <p>Discussion</p> <p>If shown to be effective, Internet-based PST will offer new possibilities to reach and treat MS patients with depressive symptoms and to improve the quality of care.</p> <p>Trial Registration</p> <p>The Dutch Cochrane Center, NTR2772</p

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level